This invention relates to compositions and methods capable of detecting cancer cells or malignant tumors in humans. More particularly, this invention relates to compositions radiolabeled with technetium-99m, Iodine-125, Iodine-131 or Iodine-123 which, when administered to a human will accumulate at cells producing hCG, hCG-like material, and a compound similar to and/or identical to the beta-chain of chorionic gonadotropin, or mixtures thereof.
The use of compositions which emit radiation at levels which can be detected after administration to the human body are well known. These compositions are utilized to visualize and/or monitor functioning of various parts of the body or are utilized diagnostically to determine the presence or absence of particular antigens, antibodies, hormones or the like. In one particular aspect of the prior art, radiolabeled antibodies are utilized to detect tumors having associated therewith carcinoembryonic antigen. As disclosed in U.S. Pat. Nos. 3,663,684, 3,867,363 and 3,927,193, I.sup.131 or I.sup.125 labeled antibodies to carcinoembryonic antigen are utilized to detect tumors which produce or are associated with carcinoembryonic antigen. It is also well known that protein molecules can be tagged with technetium-99m in order to form diagnostic agents. It has also been proposed to tag the antibody of the beta chain of human chorionic gonadotropin with peroxidase (McManus et al, Cancer Research, 36, pp. 2367-3481, September, 1976) in order to localize the antigen in malignant tumors. Furthermore, it has been proposed to label the IgG antibody to hCG with radioactive iodine in order to localize the antigen in human choriocarcinomas transplanted in hamster check pouches; Quinones et al (1971), Journal of Nuclear Medicine, Vol. 12, No. 2, pp. 69-75.
Recently, it has been found that neoplastic tissues produce and express on their surface chorionic gonadotropin, chorionic gonadotropin-like material, and a compound similar to and/or identical to the beta-chain of chorionic gonadotropin (hCG-beta subunit) or mixtures thereof, specifically to the degree where it is considered a more general marker than either carcinoembryonic antigen (CEA) or alphafetoprotein (AFP), Acevedo et al, "Detection and Prevention of Cancer", Part 2, Vol. I, H. E. Nieburgs (ED) Marcel Dekker, Inc. New York, 1978, pp. 937-979. The positive identification of chorionic gonadotropin in a heterogenous group of cancer cells and its non-detection in non-cancer cells in vitro has suggested that:
(a) this is a unique trophoblastic-like sialoglycoprotein which is synthesized de-novo by the malignant cells; PA1 (b) since CG and/or CG-like glycoprotein has been observed only in the trophoblast and human spermatozoa, its production by the cancer cells can only be explained by an expression of the information which opens the mechanism(s) for its biosynthesis, either by derepression of by an activation of the genetic control; PA1 (c) the compound is a common antigen (common denominator) of every cell with oncogenic properties. PA1 (1) An animal of a species different from the species in which the first antibody was produced is immunized with a non-immune IgG fraction (normal IgG) of immunoglobulin from an animal species used in obtaining the first antibody in order to produce a desired second antibody which binds to first antibody or: PA1 (2) Immune IgG fraction (anti-hCG-IgG) from the animal used to produce the first antibody is administered to an animal of a different species to produce a desired second antibody which binds to its first antibody.
While peroxidase-labeled or fluorescein-labeled anti-hCG-beta or anti-hCG are effective for identifying and localizing malignant cells, these labeled compositions are undesirable for in-vivo use because they do not allow for visualization by any available scintigraphy detection system and are otherwise undesirable for widespread use because they are simply an in-vitro immunohistochemical technique requiring light or electron microscopy or biopsy samples for positive identification. In addition, the use of radiolabeled antibody in scintigraphy wherein the labeled antibody binds directly to the cancer cell having its corresponding antigen can cause faint and imperfect imaging of the cancer cell or cells since the antibody usually has a limited number of binding sites. Thus, the cell may only be able to accomodate one radiolabeled antibody molecule on a single antigen site. Thus, the density of the radiolabeled molecule on the cell surface may not be sufficient to permit distinction of the cancer cell from surrounding tissues.
Accordingly, it would be highly desirable to provide a class or labeled antibodies which can be utilized in-vivo and which overcomes the disadvantages of the prior art compositions.